Selegiline's Wide Array of Potential Therapeutic Effects

Selegiline yog ib qho irreversible monoamine oxidase (MAO) B inhibitor¹. Monoamine neurotransmitters, xws li serotonin, dopamine thiab norepinephrine, yog derivatives ntawm amino acids². Lub enzyme monoamine oxidase A (MAO A) feem ntau oxidises (tawg) serotonin thiab norepinephrine hauv lub hlwb, thaum monoamine oxidase B (MAO B) feem ntau oxidises phenylethylamine, methylhistamine thiab tryptamine.³. MAO A thiab B ob leeg zom dopamine thiab tyramine³. Inhibiting MAOs nce cov nyiaj ntawm monoamine neurotransmitters hauv lub hlwb los ntawm kev tiv thaiv lawv cov kev puas tsuaj.³. MAO inhibitors (MAOIs) tuaj yeem xaiv rau A lossis B qhov sib txawv ntawm cov enzyme ntawm koob tshuaj tsawg tab sis zoo li poob kev xaiv rau ib qho tshwj xeeb MAO ntawm koob ntau dua.³. Tsis tas li ntawd, MAOIs tuaj yeem khi rau MAO reversibly lossis irreversibly rau inhibit qhov kev ua ntawm enzyme.⁴, nrog rau tom kawg tending kom muaj zog dua.

MAOIs tau txo qis hauv kev siv sijhawm dhau los vim kev txhim kho cov tshuaj uas xaiv lub hom phiaj sib txawv ntawm cov neurotransmitters, vim tias MAOIs tuaj yeem ua rau muaj zog tyramine vim inhibiting nws qhov kev puas tsuaj, thiab tyramine-induced hypertensive ntsoog tuaj yeem tshwm sim.⁵. Vim tias qhov kev pheej hmoo no, tus neeg mob noj zaub mov yuav tsum tau saib xyuas kom zoo rau cov khoom noj nplua nuj tyramine uas tsis yooj yim, thiab ntau yam tshuaj sib cuam tshuam tuaj yeem tshwm sim thaum MAOI siv nrog lwm cov tshuaj uas cuam tshuam rau cov qib neurotransmitter uas tuaj yeem ua rau muaj kev phom sij xws li mob hnyav heev. siab serotonin, los yog serotonin syndrome⁶.

Selegiline yog qhov kev tshawb pom qub, thiab tau tsim thawj zaug hauv xyoo 1962¹. Nws xaiv lub hom phiaj MAO B ntawm koob tshuaj tsawg, thiab tsis zoo li yuav ua rau muaj kev phom sij nce qib tyramine ua rau tawg thaum sib xyaw nrog cov khoom noj uas nplua nuj tyramine; xwb, nws feem ntau txo cov ntshav siab¹. Tsis tas li ntawd, nws tsis yog mob siab rau lub siab thiab zoo li ua kom lub neej expectancy nyob rau hauv Parkinson tus kab mob (PD) cov neeg mob¹. Hauv kev tshawb fawb, nws ncua qhov kev xav tau ntawm levodopa hauv PD los ntawm kwv yees li 9 lub hlis thaum piv rau cov tshuaj tiv thaiv antioxidant tocopherol, tej zaum vim yog dopamine-nce cov teebmeem ntawm cov tshuaj raws li pom nyob rau hauv post-mortem hlwb ntawm selegiline-cov neeg mob nrog nce qib dopamine.¹. Tsis tas li ntawd, selegiline los ntawm nws tus kheej txo oxidative kev nyuaj siab ua raws li ib tug neuroprotectant nrog neurotrophic thiab antiapoptotic kev ua si.¹.

Selegiline kuj tseem txhim kho lub cev muaj zog, kev ua haujlwm nco thiab kev txawj ntse hauv cov neeg mob PD⁷. Hauv cov menyuam yaus uas muaj kev tsis txaus siab / tsis txaus ntseeg (ADHD), selegiline txo cov tsos mob ADHD los ntawm kev txhim kho tus cwj pwm, saib xyuas thiab kawm cov ntaub ntawv tshiab yam tsis tau sau tseg cov kev mob tshwm sim.⁸. Hauv cov tub ntxhais hluas uas muaj kev nyuaj siab, qhov txo qis hauv cov tsos mob ntawm kev nyuaj siab yog pom siv transdermal kev tswj hwm ntawm selegiline.⁹. Thaum siv los kho mob kev nyuaj siab loj (MDD), es tsis ua rau muaj kev phiv los ntawm kev sib deev zoo li niaj hnub serotonin exposure-increasing antidepressants¹⁰, selegiline tau txais txiaj ntsig zoo nce cov qhab nia ntawm feem ntau cov kev ntsuam xyuas kev sib deev¹¹ tej zaum vim nws cov teebmeem dopaminergic.

MAO-B inhibitors xws li selegiline thiab rasagiline yuav ua rau qeeb tus nqi ntawm cov kab mob neurodegenerative.¹, thiab ob qho tib si zoo li muaj txiaj ntsig zoo sib xws hauv kev kho PD¹². Txawm li cas los xij, hauv cov qauv nas, selegiline tau siv tshuaj tiv thaiv kev ntxhov siab tsis zoo li rasagiline txawm tias ob qho tshuaj tau sib xyaw rau MAO inhibition.¹³, tawm tswv yim txawm tias tsis yog MAO inhibition cuam tshuam txog cov txiaj ntsig ntawm selegiline. Selegiline kuj nce synaptic plasticity nyob rau hauv medial prefrontal cortex ntawm nas nrog mimiced PD¹³, muaj feem cuam tshuam los ntawm kev pom zoo ntawm cov tshuaj ntawm cov tshuaj neurotrophic xws li paj hlwb kev loj hlob, lub hlwb-derived neurotrophic factor thiab glial cell-derived neurotrophic factor.¹⁴. Thaum kawg, selegiline tuaj yeem sib txawv raws li MAOI tshwj xeeb vim nws cov metabolites nthuav dav uas suav nrog l-amphetamine-zoo li thiab l-methamphetamine.¹⁵, uas tuaj yeem ua rau selegiline cov teebmeem tshwj xeeb. Txawm hais tias cov metabolites no, tau pom zoo siv los kho kev tsim txom psychostimulant thiab kev haus luam yeeb vim selegiline ntseeg tau tias muaj peev xwm tsim txom tsawg hauv chaw kho mob.¹⁵.

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